Coverage, Matching, and Beyond: New Results on Budgeted Mechanism Design

We study a type of reverse (procurement) auction problems in the presence of budget constraints. The general algorithmic problem is to purchase a set of resources, which come at a cost, so as not to exceed a given budget and at the same time maximize a given valuation function. This framework captures the budgeted version of several well known optimization problems, and when the resources are owned by strategic agents the goal is to design truthful and budget feasible mechanisms, i.e. elicit the true cost of the resources and ensure the payments of the mechanism do not exceed the budget. Budget feasibility introduces more challenges in mechanism design, and we study instantiations of this problem for certain classes of submodular and XOS valuation functions. We first obtain mechanisms with an improved approximation ratio for weighted coverage valuations, a special class of submodular functions that has already attracted attention in previous works. We then provide a general scheme for designing randomized and deterministic polynomial time mechanisms for a class of XOS problems. This class contains problems whose feasible set forms an independence system (a more general structure than matroids), and some representative problems include, among others, finding maximum weighted matchings, maximum weighted matroid members, and maximum weighted 3D-matchings. For most of these problems, only randomized mechanisms with very high approximation ratios were known prior to our results

The tyranny of utilitarian but democracy of hedonic choices

While offering choice can meet diverse consumer tastes, it can also decrease consumers’ satisfaction or motivation to choose altogether. It is unclear under which circumstances offering choice would be detrimental or beneficial for consumers. In two experiments, we find that offering utilitarian choices decreased, but offering hedonic ones increased, choice satisfaction. Offering utilitarian choices increased difficulty and depleted consumers, while offering hedonic choices increased autonomy and vitalized them. We thus suggest that the different types of choice that consumers make likely act as a moderator for the choice overload phenomenon

Key emerging issues in frontotemporal dementia.

Frontotemporal dementia (FTD) encompasses the syndromes of behavioural variant FTD (bvFTD) and primary progressive aphasia (PPA) and refers to those neurodegenerative diseases characterised by predominant pathological involvement of the frontal and temporal lobes. Recent years have witnessed major advances in the clinical characterisation of FTD, reflected in the publication of updated diagnostic criteria for bvFTD and PPA, and the discovery of new pathogenic mutations has added to the understanding of genotype-phenotype interactions and of disease mechanisms. Emerging results from longitudinal studies of familial FTD show that imaging and cognitive changes occur years before symptom onset and such studies may yield biomarkers of early disease that in turn will facilitate earlier diagnosis. The hope and (guarded) expectation is that these advances may together herald the beginning of the end of the chapter in which FTD is considered an inexorably progressive and untreatable condition.Dr Chan is funded by the Cambridge NIHR Biomedical Research Centre and receives grant income from the UK Medical Research Council, Technology Strategy Board and the Cambridge Isaac Newton Trust.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s00415-015-7880-

Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

Differentiation of Human Embryonic Stem Cells into Cells with Corneal Keratocyte Phenotype

Corneal transparency depends on a unique extracellular matrix secreted by stromal keratocytes, mesenchymal cells of neural crest lineage. Derivation of keratocytes from human embryonic stem (hES) cells could elucidate the keratocyte developmental pathway and open a potential for cell-based therapy for corneal blindness. This study seeks to identify conditions inducing differentiation of pluripotent hES cells to the keratocyte lineage. Neural differentiation of hES cell line WA01(H1) was induced by co-culture with mouse PA6 fibroblasts. After 6 days of co-culture, hES cells expressing cell-surface NGFR protein (CD271, p75NTR) were isolated by immunoaffinity adsorption, and cultured as a monolayer for one week. Keratocyte phenotype was induced by substratum-independent pellet culture in serum-free medium containing ascorbate. Gene expression, examined by quantitative RT-PCR, found hES cells co-cultured with PA6 cells for 6 days to upregulate expression of neural crest genes including NGFR, SNAI1, NTRK3, SOX9, and MSX1. Isolated NGFR-expressing cells were free of PA6 feeder cells. After expansion as a monolayer, mRNAs typifying adult stromal stem cells were detected, including BMI1, KIT, NES, NOTCH1, and SIX2. When these cells were cultured as substratum-free pellets keratocyte markers AQP1, B3GNT7, PTDGS, and ALDH3A1 were upregulated. mRNA for keratocan (KERA), a cornea-specific proteoglycan, was upregulated more than 10,000 fold. Culture medium from pellets contained high molecular weight keratocan modified with keratan sulfate, a unique molecular component of corneal stroma. These results show hES cells can be induced to differentiate into keratocytes in vitro. Pluripotent stem cells, therefore, may provide a renewable source of material for development of treatment of corneal stromal opacities. © 2013 Chan et al

Rationalizations and identity conflict following smoking relapse: a thematic analysis

Introduction: Little is known about how smokers respond cognitively and emotionally to the experience of “late” relapse after the acute withdrawal phase. This study assessed the kinds of thoughts and feelings that emerge in order to provide a basis for quantitative research assessing prevalence of different types of response and implications for future quit attempts. Methods: Face-to-face in-depth interviews were conducted among 14 people attending a quit smoking clinic in Malaysia who had relapsed after at least 6 weeks of abstinence. Transcripts were analyzed using thematic analysis to enable emergence of important aspects of the experience. Results: Following relapse, smokers often engaged in rationalizations and activities to minimize worry about the harmful effects of smoking by switching to a lower-tar cigarette, reducing the number of cigarette smoked, attempting to reduce cigarette smoke inhalation, comparing themselves with other smokers, and minimizing the health risks associated with smoking. In some cases, smokers retained a “non-smoker” identity despite having relapsed. Conclusion: Smoking relapsers rationalize their failure to quit and minimize their health risk in order to protect their image as non-smokers while it remains a source of identity conflict

Output specifications for PPP projects : lessons from case studies

The 3rd International Postgraduate Conference on Infrastructure and Environment is organized by the Faculty of Construction & Land Use of The Hong Kong Polytechnic University on 11 and 12 July 2011 in Hong Kong.Author name used in this publication: Patrick T. I. LamVersion of RecordPublishe

Multiple morbidity across the lifespan in people with Down syndrome or intellectual disabilities: a population-based cohort study using electronic health records.

BACKGROUND: The Down syndrome phenotype is well established, but our understanding of its morbidity patterns is limited. We comprehensively estimated the risk of multiple morbidity across the lifespan in people with Down syndrome compared with the general population and controls with other forms of intellectual disability. METHODS: In this matched population-based cohort-study design, we used electronic health-record data from the UK Clinical Practice Research Datalink (CRPD) from Jan 1, 1990, to June 29, 2020. We aimed to explore the pattern of morbidities throughout the lifespan of people with Down syndrome compared with people with other intellectual disabilities and the general population, to identify syndrome-specific health conditions and their age-related incidence. We estimated incidence rates per 1000 person-years and incidence rate ratios (IRRs) for 32 common morbidities. Hierarchical clustering was used to identify groups of associated conditions using prevalence data. FINDINGS: Between Jan 1, 1990, and June 29, 2020, a total of 10 204 people with Down syndrome, 39 814 controls, and 69 150 people with intellectual disabilities were included. Compared with controls, people with Down syndrome had increased risk of dementia (IRR 94·7, 95% CI 69·9-128·4), hypothyroidism (IRR 10·6, 9·6-11·8), epilepsy (IRR 9·7, 8·5-10·9), and haematological malignancy (IRR 4·7, 3·4-6·3), whereas asthma (IRR 0·88, 0·79-0·98), cancer (solid tumour IRR 0·75, 0·62-0·89), ischaemic heart disease (IRR 0·65, 0·51-0·85), and particularly hypertension (IRR 0·26, 0·22-0·32) were less frequent in people with Down syndrome than in controls. Compared to people with intellectual disabilities, risk of dementia (IRR 16·60, 14·23-19·37), hypothyroidism (IRR 7·22, 6·62-7·88), obstructive sleep apnoea (IRR 4·45, 3·72-5·31), and haematological malignancy (IRR 3·44, 2·58-4·59) were higher in people with Down syndrome, with reduced rates for a third of conditions, including new onset of dental inflammation (IRR 0·88, 0·78-0·99), asthma (IRR 0·82, 0·73-0·91), cancer (solid tumour IRR 0·78, 0·65-0·93), sleep disorder (IRR 0·74, 0·68-0·80), hypercholesterolaemia (IRR 0·69, 0·60-0·80), diabetes (IRR 0·59, 0·52-0·66), mood disorder (IRR 0·55, 0·50-0·60), glaucoma (IRR 0·47, 0·29-0·78), and anxiety disorder (IRR 0·43, 0·38-0·48). Morbidities in Down syndrome could be categorised on age-related incidence trajectories, and their prevalence clustered into typical syndromic conditions, cardiovascular diseases, autoimmune disorders, and mental health conditions. INTERPRETATION: Multiple morbidity in Down syndrome shows distinct patterns of age-related incidence trajectories and clustering that differ from those found in the general population and in people with other intellectual disabilities, with implications for provision and timing of health-care screening, prevention, and treatment for people with Down syndrome. FUNDING: The European Union's Horizon 2020 Research and Innovation Programme, the Jérôme Lejeune Foundation, the Alzheimer's Society, the Medical Research Council, the Academy of Medical Sciences, the Wellcome Trust, and William Harvey Research Limited

Algebraic K-theory of endomorphism rings

We establish formulas for computation of the higher algebraic $K$-groups of the endomorphism rings of objects linked by a morphism in an additive category. Let ${\mathcal C}$ be an additive category, and let Y\ra X be a covariant morphism of objects in ${\mathcal C}$. Then $K_n\big(_{\mathcal C}(X\oplus Y)\big)\simeq K_n\big(_{{\mathcal C},Y}(X)\big)\oplus K_n\big(_{\mathcal C}(Y)\big)$ for all $1\le n\in \mathbb{N}$, where $_{{\mathcal C},Y}(X)$ is the quotient ring of the endomorphism ring $_{\mathcal C}(X)$ of $X$ modulo the ideal generated by all those endomorphisms of $X$ which factorize through $Y$. Moreover, let $R$ be a ring with identity, and let $e$ be an idempotent element in $R$. If $J:=ReR$ is homological and $_RJ$ has a finite projective resolution by finitely generated projective $R$-modules, then $K_n(R)\simeq K_n(R/J)\oplus K_n(eRe)$ for all $n\in \mathbb{N}$. This reduces calculations of the higher algebraic $K$-groups of $R$ to those of the quotient ring $R/J$ and the corner ring $eRe$, and can be applied to a large variety of rings: Standardly stratified rings, hereditary orders, affine cellular algebras and extended affine Hecke algebras of type $\tilde{A}$.Comment: 21 pages. Representation-theoretic methods are used to study the algebraic K-theory of ring

Impact of maternal cigarette smoke exposure on brain inflammation and oxidative stress in male mice offspring

Maternal cigarette smoke exposure (SE) during gestation can cause lifelong adverse effects in the offspring's brain. Several factors may contribute including inflammation, oxidative stress and hypoxia, whose changes in the developing brain are unknown. Female Balb/c mice were exposed to cigarette smoke prior to mating, during gestation and lactation. Male offspring were studied at postnatal day (P) 1, P20 and 13 weeks (W13). SE dams had reduced inflammatory mediators (IL-1β, IL-6 and toll like receptor (TLR)4 mRNA), antioxidant (manganese superoxide dismutase (MnSOD)), and increased mitochondrial activities (OXPHOS-I, III and V) and protein damage marker nitrotyrosine. Brain hypoxia-inducible factor (HIF)1α and its upstream signalling molecule early growth response factor (EGR)1 were not changed in the SE dams. In the SE offspring, brain IL-1R, IL-6 and TLR4 mRNA were increased at W13. The translocase of outer mitochondrial membrane, and MnSOD were reduced at W13 with higher nitrotyrosine staining. HIF-1α was also increased at W13, although EGR1 was only reduced at P1. In conclusion, maternal SE increased markers of hypoxia and oxidative stress with mitochondrial dysfunction and cell damage in both dams and offspring, and upregulated inflammatory markers in offspring, which may render SE dams and their offspring vulnerable to additional brain insults